Prognostic and predictive role of circulating tumor DNA (ctDNA) in stage III colon cancer treated with celecoxib: Findings from CALGB (Alliance)/SWOG 80702.
Bibliographic record
Abstract
LBA14 Background: CALGB/SWOG 80702 previously showed that the addition of celecoxib to standard adjuvant chemotherapy with FOLFOX did not significantly improve disease-free survival (DFS) in patients with stage III colon cancer. Here, we evaluated the prognostic and predictive value of ctDNA in identifying a subpopulation of patients who may benefit from celecoxib. Methods: In the subset of patients with adequate biospecimens who participated in CALGB/SWOG 80702, a randomized phase III trial of 3 versus 6 months of adjuvant 5-FU, leucovorin, oxaliplatin (FOLFOX) +/- celecoxib, ctDNA assessment was performed using a clinically validated, tumor-informed 16-plex mPCR-NGS assay (Signatera(TM), Natera, Inc.) after surgery and before the start of adjuvant therapy (baseline). The Kaplan-Meier method was used to describe the distribution of survival time based on ctDNA positivity and log-rank testing was performed. Cox proportional hazards models were used to examine unadjusted associations between ctDNA positivity and disease-free (DFS) and overall survival (OS). Two-sided P values equal to or less than 0.05 were considered statistically significant, except for interaction P values (tested with a likelihood ratio). Results: In total, 1,011 of the 2,526 patients who participated in 80702 had ctDNA testing results from baseline; 189 were ctDNA positive (18.7%). ctDNA positivity associated with male sex, higher T stage, and N2 (versus N1) stage. ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR] 6.52 [95% confident interval (CI) 5.09-8.34; p<0.0001] and OS (HR 6.28 [95% CI 4.63-8.51; p<0.0001]). Three-year DFS was 86.6% in ctDNA-negative cases and 36.8% in ctDNA-positive cases. Among patients who were ctDNA negative, celecoxib use was not significantly associated with worse DFS as compared to placebo (HR 0.75 [95% CI 0.54-1.05; p=0.095]) with a three-year DFS of 87.7% versus 85.5%, respectively. Among ctDNA-positive patients, celecoxib significantly improved DFS compared to placebo (HR 0.59 [95% CI 0.42-0.85; p=0.004]) with a three-year DFS of 44.1% versus 26.6% (P interaction = 0.25). Similar results were seen for overall survival with a hazard ratio of 0.86 (95% CI 0.56-1.33; p=0.49) for ctDNA negative cases and 0.63 (95% CI 0.41-0.96; p=0.028) for ctDNA-positive cases for celecoxib versus placebo (P interaction = 0.28). Conclusion: In a randomized phase III adjuvant therapy trial for stage III colon cancer, ctDNA was highly prognostic of DFS and OS. ctDNA positivity also appeared predictive of the benefit of adjuvant celecoxib for DFS and OS. These results suggest a potential role for ctDNA in determining which patients should consider celecoxib in addition to standard FOLFOX adjuvant therapy. Clinical trial information: NCT01150045 .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".